Persistent epigenetic modulation by radiation exposure/insults in mammalian cells

Resumo

Effects of radiation in biological systems are quite interesting. Interaction of radiation to epigenetic mechanisms has been also demonstrated earlier. The aim of this review is to sketch a current scenario on radiation exposure/insults on the epigenetic mechanisms in mammalian cells. Evidence from the databases, mainly from Pubmed and Science Direct were considered. Findings suggest that radiation has a dose and timedependent effect in our body. Cells and tissues from different sources have differential responses towards radiation insults. Although radiation has impacts on epigenetic modulation, but it has beneficial combinatorial effects with a number of epigenetic modalities. Radiation has both bad and good impacts on epigenetic mechanisms.

Referências

1. Abdelfatah, E.; Kerner, Z.; Nanda, N.; Ahuja, N.
2. Epigenetic therapy in gastrointestinal cancer:
3. The right combination. Ther. Adv.
4. Gastroenterol., v. 9, p. 560-579, 2016.
5. https://doi.org/10.1177/1756283X1664424
6. Amendola, P. G.; Zaghet, N.; Ramalho, J. J.;
7. Johansen, J. V.; Boxem, M.; Salcini, A. E. JMJD5/KDM8 regulates H3K36me2 and is
8. required for late steps of homologous
9. recombination and genome integrity. PLoS
10. Genet., v. 13, e1006632, 2017.
11. https://doi.org/10.1371/journal.pgen.10066
12. An, Y. S.; Kim, M. R.; Lee, S. S.; Lee, Y. S.;
13. Chung, E.; Song, J. Y.; Lee, J.; Yi, J. Y. TGF-β
14. signaling plays an important role in resisting
15. γ-irradiation. Exp. Cell Res., v. 319, p. 466-
16. , 2013.
17. Bar-Sela, G.; Jacobs, K. M.; Gius, D. Histone
18. deacetylase inhibitor and demethylating
19. Epigenetic modulation by radiation exposure/insults 595
20. Braz. J. Biol. Sci., 2018, v. 5, No. 10, p. 589-598.
21. agent chromatin compaction and the
22. radiation response by cancer cells. Cancer J.,
23. v. 13, p. 65-69, 2007.
24. Belinsky, S. A.; Klinge, D. M.; Liechty, K. C.;
25. March, T. H.; Kang, T.; Gilliland, F. D.; Sotnic,
26. N.; Adamova, G.; Rusinova, G.; Telnov, V.
27. Plutonium targets the p16 gene for
28. inactivation by promoter hypermethylation
29. in human lung adenocarcinoma.
30. Carcinogenesis, v. 25, p. 1063-1067, 2004.
31. Biade, S.; Stobbe, C. C.; Boyd, J. T.; Chapman, J.
32. D. Chemical agents that promote chromatin
33. compaction radiosensitize tumour cells. Int.
34. J. Rad. Biol., v. 77, p. 1033-1042, 2001.
35. Boerma, M.; Sridharan, V.; Mao, X. W.; Nelson,
36. G. A.; Cheema, A. K.; Koturbash, I.; Singh, S. P.;
37. Tackett, A. J.; Hauer-Jensen, M. Effects of
38. ionizing radiation on the heart. Mutat. Res.-
39. Rev. Mutat., v. 770, p. 319-327, 2016.
40. Burk, U.; Schubert, J.; Wellner, U.;
41. Schmalhofer, O.; Vincan, E.; Spaderna, S.;
42. Brabletz, T. A reciprocal repression between
43. ZEB1 and members of the miR-200 family
44. promotes EMT and invasion in cancer cells.
45. EMBO Rep., v. 9, p. 582-589, 2008.
46. https://doi.org/10.1038/embor.2008.74
47. Bussing, I.; Slack, F. J.; Grosshans, H. Let-7
48. microRNAs in development, stem cells and
49. cancer. Trends Mol. Med., v. 14, p. 400-409,
50. Chaudhry, M. A.; Omaruddin, R. A. Differential
51. DNA methylation alterations in radiationsensitive and -resistant cells. DNA Cell Biol.,
52. v. 31, p. 908-916, 2012.
53. https://doi.org/10.1089/dna.2011.1509
54. Dahle, J.; Kvam, E. Induction of delayed
55. mutations and chromosomal instability in
56. fibroblasts after UVA-, UVB-, and X-radiation.
57. Cancer Res., v. 63, p. 1464-1469, 2003.
58. Deng, S.; Calin, G. A.; Croce, C. M.; Coukos, G.;
59. Zhang, L. Mechanisms of microRNA
60. deregulation in human cancer. Cell Cycle,
61. v. 7, p. 2643-2646, 2008.
62. Dent, P.; Yacoub, A.; Fisher, P. B.; Hagan, M. P.;
63. Grant, S. MAPK pathways in radiation
64. responses. Oncogene, v. 22, p. 5885-5896,
65. Dickey, J. S.; Zemp, F. J.; Martin, O. A.;
66. Kovalchuk, O. The role of miRNA in the direct
67. and indirect effects of ionizing radiation.
68. Radiat. Environ. Biophys., v. 50, p. 491-499,
69. Engels, B. M.; Hutvagner, G. Principles and
70. effects of microRNA-mediated posttranscriptional gene regulation. Oncogene,
71. v. 25, p. 6163-6169, 2006.
72. Espada, J.; Esteller, M. Epigenetic control of
73. nuclear architecture. Cell Mol. Life Sci., v. 64,
74. p. 449-457, 2007.
75. Fokas, E.; Yoshimura, M.; Prevo, R.; Higgins,
76. G.; Hackl, W.; Maira, S. M.; Bernhard, E. J.;
77. McKenna, W. G.; Muschel, R. J. NVP-BEZ235
78. and NVP-BGT226, dual phosphatidylinositol
79. -kinase/mammalian target of rapamycin
80. inhibitors, enhance tumor and endothelial
81. cell radiosensitivity. Radiat. Oncol., 7:48,
82. Ghosh, S. P.; Singh, R.; Chakraborty, K.;
83. Kulkarni, S.; Uppal, A.; Luo, Y.; Kaur, P.;
84. Pathak, R.; Kumar, K. S.; Hauer-Jensen, M.;
85. Cheema, A. K. Metabolomic changes in
86. gastrointestinal tissues after whole body
87. radiation in a murine model. Mol. Biosyst.,
88. v. 9, p. 723-731, 2013.
89. Gravina, G. L.; Festuccia, C.; Marampon, F.;
90. Popov, V. M.; Pestell, R. G.; Zani, B. M.;
91. Tombolini, V. Biological rationale for the use
92. of DNA methyltransferase inhibitors as new
93. strategy for modulation of tumor response to
94. chemotherapy and radiation. Molec. Cancer,
95. :305, 2010.
96. Grelier, G.; Voirin, N.; Ay, A. S.; Cox, D. G.;
97. Chabaud, S.; Treilleux, I.; Léon-Goddard, S.;
98. Rimokh, R.; Mikaelian, I.; Venoux, C.; Puisieux,
99. A.; Lasset, C.; Moyret-Lalle, C. Prognostic
100. value of Dicer expression in human breast
101. cancers and association with the
102. mesenchymal phenotype. Br. J. Cancer,
103. v. 101, no. 4, p. 673-683, 2009.
104. Guo, X.; Liao, Q.; Chen, P.; Li, X.; Xiong, W.; Ma,
105. J.; Li, X.; Luo, Z.; Tang, H.; Deng, M.; Zheng, Y.;
106. Wang, R.; Zhang, W.; Li. G. The microRNAprocessing enzymes: Drosha and Dicer can
107. predict prognosis of nasopharyngeal
108. carcinoma. J. Cancer Res. Clin. Oncol.,
109. v. 138, p. 49-56, 2012.
110. https://doi.org/10.1007/s00432-011-1058-
111. Hall, E.; Giaccia, A. Radiobiology for the
112. radiologist. 7. ed. Philadelphia: Lippincott
113. Williams and Wilkins, 2011.
114. Ilnytskyy, Y.; Zemp, F. J.; Koturbash, I.;
115. Kovalchuk, O. Altered microRNA expression
116. patterns in irradiated hematopoietic tissues
117. suggest a sex-specific protective mechanism.
118. Biochem. Biophys. Res. Commun., v. 377,
119. p. 41-45, 2008.
120. Islam
121. Braz. J. Biol. Sci., 2018, v. 5, No. 10, p. 589-598.
122. Jaklevic, B.; Uyetake, L.; Wichmann, A.; Bilak,
123. A.; English, C. N.; Su, T. T. Modulation of
124. ionizing radiation-induced apoptosis by
125. bantam microRNA in Drosophila. Develop.
126. Biol., v. 320, p. 122-130, 2008.
127. Johnson, S. M.; Grosshans, H.; Shingara, J.;
128. Byrom, M.; Jarvis, R.; Cheng, A.; Labourier, E.;
129. Reinert, K. L.; Brown, D.; Slack, F. J. RAS is
130. regulated by the let-7 microRNA family. Cell,
131. v. 120, p. 635-647, 2005.
132. Joiner, M. C.; Lambin, P.; Malaise, E. P.;
133. Robson, T.; Arrand, J. E.; Skov, K. A.; Marples,
134. B. Hypersensitivity to very-low single
135. radiation doses: Its relationship to the
136. adaptive response and induced
137. radioresistance. Mutat. Res., v. 358, p. 171-
138. , 1996.
139. Jones, P. A. Functions of DNA methylation:
140. Islands, start sites, gene bodies and beyond.
141. Nat. Rev. Genet., v. 13, p. 484-492, 2012.
142. Kalinich, J. F.; Catravas, G. N.; Snyder, S. L. The
143. effect of γ-radiation on DNA methylation.
144. Radiat. Res., v. 117, p. 185-197, 1989.
145. Karube, Y.; Tanaka, H.; Osada, H.; Tomida, S.;
146. Tatematsu, Y.; Yanagisawa, K.; Yatabe, Y.;
147. Takamizawa, J.; Miyoshi, S.; Mitsudomi, T.;
148. Takahashi T. Reduced expression of Dicer
149. associated with poor prognosis in lung
150. cancer patients. Cancer Sci., v. 96, p. 111-
151. , 2005.
152. Kim, G. J.; Fiskum, G. M.; Morgan, W. F. A role
153. for mitochondrial dysfunction in
154. perpetuating radiation-induced genomic
155. instability. Cancer Res., v. 66, p. 10377-
156. , 2006.
157. Koturbash, I.; Boyko, A.; Rodriguez-Juarez, R.;
158. McDonald, R. J.; Tryndyak, V. P.; Kovalchuk, I.;
159. Pogribny, I. P.; Kovalchuk, O. Role of
160. epigenetic effectors in maintenance of the
161. long-term persistent bystander effect in
162. spleen in vivo. Carcinogenesis, v. 28,
163. p. 1831-1838, 2007.
164. Koturbash, I.; Miousse, I. R.; Sridharan, V.;
165. Nzabarushimana, E.; Skinner, C. M.; Melnyk, S.
166. B.; Pavliv, O.; Hauer-Jensen, M.; Nelson, G. A.;
167. Boerma, M. Radiation-induced changes in
168. DNA methylation of repetitive elements in
169. the mouse heart. Mutat. Res.-Fund. Mol. M.,
170. v. 787, p. 43-53, 2016.
171. Koturbash, I.; Pogribny, I.; Kovalchuk, O.
172. Stable loss of global DNA methylation in the
173. radiation-target tissue: A possible
174. mechanism contributing to radiation
175. carcinogenesis? Biochem. Bioph. Res. Co.,
176. v. 337, p. 526-533, 2005.
177. Koturbash, I.; Zemp, F.; Kolb, B.; Kovalchuk,
178. O. Sex-specific radiation-induced
179. microRNAome responses in the
180. hippocampus, cerebellum and frontal cortex
181. in a mouse model. Mutat. Res., v. 722, p. 114-
182. , 2011.
183. Kovalchuk, O.; Burke, P.; Besplug, J.; Slovack,
184. M.; Filkowski, J.; Pogribny, I. Methylation
185. changes in muscle and liver tissues of male
186. and female mice exposed to acute and
187. chronic low-dose X-ray-irradiation. Mutat.
188. Res., v. 548, p. 75-84, 2004.
189. Kraemer, A.; Anastasov, N.; Angermeier, M.;
190. Winkler, K.; Atkinson, M. J.; Moertl, S.
191. MicroRNA-mediated processes are essential
192. for the cellular radiation response. Radiat.
193. Res., v. 176, p. 575-586, 2011.
194. Kumar, M. S.; Pester, R. E.; Chen, C. Y.; Lane,
195. K.; Chin, C.; Lu, J.; Kirsch, D. G.; Golub, T. R.;
196. Jacks, T. Dicer1 functions as a
197. haploinsufficient tumor suppressor. Genes
198. Dev., v. 23, p. 2700-2704, 2009.
199. https://doi.org/10.1101/gad.1848209
200. Kutanzi, K. R.; Lumen, A.; Koturbash, I.;
201. Miousse, I. R. Pediatric exposures to ionizing
202. radiation: Carcinogenic considerations. Int. J.
203. Env. Res. Pub. Health, v. 13, no. 11, p. 1057,
204. https://doi.org/10.3390/ijerph13111
205. Lee, K.-F.; Chen, Y.-C.; Hsu, P. W.-C.; Liu, I. Y.;
206. Wu, L. S.-H. MicroRNA expression profiling
207. altered by variant dosage of radiation
208. exposure. BioMed Res. Int., v. 2014, Article
209. ID 456323, 10 p., 2014. https://doi.org/
210. 1155/2014/456323
211. Lin, R. J.; Lin, Y. C.; Chen, J.; Kuo, H. H.; Chen, Y.
212. Y.; Diccianni, M. B.; London, W. B.; Chang,
213. C. H.; Yu, A. L. MicroRNA signature and
214. expression of Dicer and Drosha can predict
215. prognosis and delineate risk groups in
216. neuroblastoma. Cancer Res., v. 70, p. 7841-
217. , 2010. https://doi.org/10.1158/0008-
218. CAN-10-0970
219. Luzhna, L.; Kovalchuk, O. Modulation of DNA
220. methylation levels sensitizes doxorubicinresistant breast adenocarcinoma cells to
221. radiation-induced apoptosis. Biochem.
222. Biophys. Res. Commun., v. 392, p. 113-117,
223. https://doi.org/10.1016/j.bbrc.2009.
224. 093
225. Ma, S.; Liu, X.; Jiao, B.; Yang, Y.; Liu, X. Lowdose radiation-induced responses: Focusing
226. Epigenetic modulation by radiation exposure/insults 597
227. Braz. J. Biol. Sci., 2018, v. 5, No. 10, p. 589-598.
228. on epigenetic regulation. Int. J. Radiat. Biol.,
229. v. 86, p. 517-528, 2010. https://doi.org/
230. 3109/09553001003734592
231. Mailand, N.; Bekker-Jensen, S.; Faustrup, H.;
232. Melander, F.; Bartek, J.; Lukas, C.; Lukas, J.
233. RNF8 ubiquitylates histones at DNA doublestrand breaks and promotes assembly of
234. repair proteins. Cell, v. 131, p. 887-900,
235. Marta, G. N.; Garicochea, B.; Carvalho, A. L.;
236. Real, J. M.; Kowalski, L. P. MicroRNAs, cancer
237. and ionizing radiation: Where are we? Rev.
238. Assoc. Med. Bras., v. 61, p. 275-281, 2015.
239. https://doi.org/10.1590/1806-9282.61.03.
240. Martello, G.; Rosato, A.; Ferrari, F.; Manfrin,
241. A.; Cordenonsi, M.; Dupont, S.; Enzo, E.;
242. Guzzardo, V.; Rondina, M.; Spruce, T.; Parenti,
243. A. R.; Daidone, M. G.; Bicciato, S.; Piccolo, S. A
244. MicroRNA targeting dicer for metastasis
245. control. Cell, v. 141, p. 1195-1207, 2010.
246. https://doi.org/10.1016/j.cell.2010.05.017
247. Maxwell, C. A.; Fleisch, M. C.; Costes, S. V.;
248. Erickson, A. C.; Boissiere, A.; Gupta, R.;
249. Ravani, S. A.; Parvin, B.; Barcellos-Hoff, M. H.
250. Targeted and non-targeted effects of ionizing
251. radiation that impact genomic instability.
252. Cancer Res., v. 68, p. 8304-8311, 2008.
253. Miousse, I. R.; Shao, L.; Chang, J.; Feng, W.;
254. Wang, Y.; Allen, A. R.; Turner, J.; Stewart, B.;
255. Raber, J.; Zhou, D.; Koturbash, I. Exposure to
256. low-dose Fe-56-ion radiation induces longterm epigenetic alterations in mouse bone
257. marrow hematopoietic progenitor and stem
258. cells. Radiat. Res., v. 182, p. 92-101, 2014.
259. Miousse, I. R.; Tobacyk, J.; Melnyk, S.; James,
260. S. J.; Cheema, A. K.; Boerma, M.; Hauer-Jensen,
261. M.; Koturbash, I. One-carbon metabolism and
262. ionizing radiation: a multifaceted interaction.
263. Bio. Mol. Concepts, v. 8, p. 83-92, 2017.
264. Mott, J. L.; Kurita, S.; Cazanave, S. C.; Bronk, S.
265. F.; Werneburg, N. W.; Fernandez-Zapico, M. E.
266. Transcriptional suppression of mir-29b1/mir-29a promoter by c-Myc, hedgehog, and
267. NF-kappaB. J. Cell Biochem., v. 110, p. 1155-
268. , 2010
269. Pfeifer, G. P.; Rauch, T. A. DNA methylation
270. patterns in lung carcinomas. Semin. Cancer
271. Biol., v. 19, p. 181-187, 2009.
272. Piovan, C.; Palmieri, D.; Di Leva, G.; Braccioli,
273. L.; Casalini, P.; Nuovo, G.; Tortoreto, M.;
274. Sasso, M.; Plantamura, I.; Triulzi, T.; Taccioli,
275. C.; Tagliabue, E.; Iorio, M. V.; Croce, C. M.
276. Oncosuppressive role of p53-induced miR205 in triple negative breast cancer. Mol.
277. Oncol., v. 6, p. 458-472, 2012.
278. Pogrlbny, I.; Koturbash, I.; Tryndyak, V.;
279. Hudson, D.; Stevenson, S. M. L.; Sedelnikova,
280. O.; Bonner, W.; Kovalchuk, O. Fractionated
281. low-dose radiation exposure leads to
282. accumulation of DNA damage and profound
283. alterations in DNA and histone methylation
284. in the murine thymus. Mol. Cancer Res., v. 3,
285. p. 553-561, 2005.
286. Pollack, B. P.; Sapkota, B.; Boss, J. M.
287. Ultraviolet radiationinduced transcription is
288. associated with gene-specific histone
289. acetylation. Photochem. Photobiol., v. 85,
290. p. 652-662, 2009.
291. Prior, S.; Miousse, I. R.; Nzabarushimana, E.;
292. Pathak, R.; Skinner, C.; Kutanzi, K. R.; Allen, A.
293. R.; Raber, J.; Tackett, A. J.; Hauer-Jensen, M.;
294. Nelson, G. A.; Koturbash, I. Densely ionizing
295. radiation affects DNA methylation of
296. selective LINE-1 elements. Environ. Res.,
297. v. 150, p. 470-481, 2016.
298. Qiu, H.; Yashiro, M.; Shinto, O.; Matsuzaki, T.;
299. Hirakawa, K. DNA methyltransferase
300. inhibitor 5-aza-CdR enhances the
301. radiosensitivity of gastric cancer cells.
302. Cancer Sci., v. 1, p. 181-188, 2009.
303. Ree, A.; Dueland, S.; Folkvord, S.; Hole, K.;
304. Seierstad, T.; Johansen, M.; Abrahamsen, T.
305. W.; Flatmark, K. Vorinostat, a histone
306. deacetylase inhibitor, combined with pelvic
307. palliative radiotherapy for gastrointestinal
308. carcinoma: the pelvic radiation and
309. vorinostat (PRAVO) phase I study. Lancet
310. Oncol., v. v. 11, p. 459-464, 2010.
311. Rhodes, L. V.; Nitschke, A. M.; Segar, H. C.;
312. Martin, E. C.; Driver, J. L.; Elliott, S.; Nam, S. Y.;
313. Li, M.; Nephew, K. P.; Burow, M. E.; CollinsBurow, B. M. The histone deacetylase
314. inhibitor trichostatin A alters microRNA
315. expression profiles in apoptosis-resistant
316. breast cancer cells. Oncol. Rep., v. 27, p. 10-
317. , 2012. https://doi.org/10.3892/
318. or.2011.1488
319. Rivera, S.; Leteur, C.; Mégnin, F.; Law, F.;
320. Martins, I.; Kloos, I.; Depil, S.; Modjtahedi, N.;
321. Perfettini, J. L.; Hennequin, C.; Deutsch, E.
322. Time dependent modulation of tumor
323. radiosensitivity by a pan HDAC inhibitor:
324. abexinostat. Oncotarget, v. 8, p. 56210-
325. , 2017.
326. Sak, A.; Kübler, D.; Bannik, K.; Groneberg, M.;
327. Strunz, S.; Kriehuber, R.; Stuschke, M.
328. Epigenetic silencing and activation of
329. transcription: Influence on the radiation
330. Islam
331. Braz. J. Biol. Sci., 2018, v. 5, No. 10, p. 589-598.
332. sensitivity of glioma cell lines. Int. J. Radiat.
333. Biol., v. 93, no. 5, p. 494-506, 2017.
334. https://doi.org/10.1080/09553002.2017.12
335. Shogren-Knaak, M.; Ishii, H.; Sun, J. M.; Pazin,
336. M. J.; Davie, J. R.; Peterson, C. L. Histone H4-
337. K16 acetylation controls chromatin structure
338. and protein interactions. Science, v. 311,
339. no. 5762, p. 844-847, 2006. https://doi.org/
340. 1126/science.1124000
341. Simone, N. L.; Soule, B. P; Ly, D.; Saleh, A. D.;
342. Savage, J. E.; Degraff, W.; Cook, J.; Harris, C. C.;
343. Gius, D.; Mitchell, J. B. Ionizing radiationinduced oxidative stress alters miRNA
344. expression. PLoS One, 4:e6377, 2009.
345. https://doi.org/10.1371/journal.pone.00063
346. Strickland, F. M.; Richardson, B. C.
347. Epigenetics in human autoimmunity
348. (Epigenetics in autoimmunity-DNA
349. methylation in systemic lupus erythematosus
350. and beyond). Autoimmunity, v. 41, no. 4,
351. p. 278-286, 2008. https://doi.org/10.1080/
352. Surova, O.; Akbar, N. S.; Zhivotovsky, B.
353. Knock-down of core proteins regulating
354. microRNA biogenesis has no effect on
355. sensitivity of lung cancer cells to ionizing
356. radiation. PLoS One, v. 7, no. 3, e33134,
357. https://doi.org/10.1371/journal.pone.
358. Tarasov, V.; Jung, P.; Verdoodt, B.; Lodygin,
359. D.; Epanchintsev, A.; Menssen, A.; Meister, G.;
360. Hermeking, H. Differential regulation of
361. microRNAs by p53 revealed by massively
362. parallel sequencing: miR-34a is a p53 target
363. that induces apoptosis and G1-arrest. Cell
364. Cycle, v. 6, p. 1586-1593, 2007.
365. https://doi.org/10.4161/cc.6.13.4436
366. Valinciute, G.; Weigel, C.; Veldwijk, M. R.;
367. Oakes, C. C.; Herskind, C.; Wenz, F.; Plass, C.;
368. Schmezer, P.; Popanda, O. BET-bromodomain
369. inhibitors modulate epigenetic patterns at
370. the diacylglycerol kinase alpha enhancer
371. associated with radiation-induced fibrosis.
372. Radiother. and Oncol., v. 125, no. 1, p. 168-
373. , 2017. https://doi.org/10.1016/j.radonc.
374. 08.028
375. Vaquero, A.; Loyola, A.; Reinberg, D. The
376. constantly changing face of chromatin. Sci.
377. Aging Knowl. Environ., v. 2003, no. 14,
378. https://doi.org/10.1126/sageke.2003.
379. re4
380. Veuger, S. J.; Hunter, J. E.; Durkacz, B. W.
381. Ionizing radiation-induced NF-kappaB
382. activation requires PARP-1 function to confer
383. radioresistance. Oncogene, v. 28, p. 832-842,
384. Wang, Y.; Medvid, R.; Melton, C.; Jaenisch, R.;
385. Blelloch, R. DGCR8 is essential for microRNA
386. biogenesis and silencing of embryonic stem
387. cell self-renewal. Nat. Genet., v. 39, p. 380-
388. , 2007.
389. Yang, A. Y.; Lee, J. H.; Shu, L.; Zhang, C.; Su, Z.-
390. Y.; Lu, Y.; Huang, M.-T.; Ramirez, C.; Pung, D.;
391. Huang, Y.; Verzi, M.; Hart, R. P.; Kong, A.-N. T.
392. Genome-wide analysis of DNA methylation in
393. UVB- and DMBA/TPA-induced mouse skin
394. cancer models. Life Sci., v. 113, p. 45-54,
395. https://doi.org/10.1016/j.lfs.2014.
396. 031
397. Yu, Y.; Waters, R. Histone acetylation,
398. chromatin remodelling and nucleotide
399. excision repair: Hint from the study on MFA2
400. in Saccharomyces cerevisiae. Cell Cycle, v. 4,
401. p. 1043-1045, 2005.
402. Zhan, M.; Han, Z. C. Phosphatidylinositide 3-
403. kinase/AKT in radiation responses. Histol.
404. Histopathol., v. 19, p. 915-923, 2004.
405. Zhao, L.; Lu, X.; Cao, Y. MicroRNA and signal
406. transduction pathways in tumor radiation
407. response. Cell. Signal., v. 25, no. 7, p. 1625-
408. , 2013. https://doi.org/10.1016/
409. j.cellsig.2013.04.004